Molecular Diversity and Functional Implications of Mammalian Choline Acetyltransferases in Neuronal and Non-Neuronal Cells
Year: 2026
Type: article
Abstract: Acetylcholine (ACh) is the first identified neurotransmitter and an evolutionarily conserved signaling molecule. Although its role in classical synaptic transmission within the central and peripheral nervous systems has been extensively studied, growing evidence indicates that cholinergic signaling extends beyond neuronal synapses and operates in a broad range of non-neuronal cells. Thus, the cholinergic system represents a complex and widely distributed signaling network with both neuronal and non-neuronal components. Within the nervous system, cholinergic neurons display marked molecular heterogeneity, largely driven by the genomic organization and alternative splicing of the choline acetyltransferase (ChAT) gene. Distinct ChAT mRNA splice variants contribute to region- and cell-type specific cholinergic phenotypes in central and peripheral neurons, including the enteric nervous system, which exemplifies a highly autonomous peripheral cholinergic network. Beyond the nervous system, non-neuronal cholinergic signaling has been identified in epithelial, cardiac, immune, and other cell types, where ACh acts as an autocrine and paracrine regulator of key physiological processes. This review summarizes current knowledge on ACh biosynthesis, focusing on ChAT and its splice variants as molecular determinants of cholinergic diversity and function across neuronal and non-neuronal contexts.
DOI: 10.3390/ijms27094034
Authors: Desislava Marinova, Stefan Trifonov
Institution: Medical University Pleven
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7160030324
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